The objective of this research program is to define the interrelationships between fatty acid and ketone body oxidation in heart. Myocardium utilizes fatty acid as the principal metabolic fuel; however, when presented with high concentrations of ketone bodies and fatty acid in blood, the myocardium utilizes ketone bodies. Both the uptake and oxidation of fatty acids are inhibited under these conditions. With these observations in mind the steady state levels of CoA and carnitine as well as some of their principal acyl derivatives are being measured in the hearts and livers of diabetic and normal rats and in rat hearts perfused with fatty acids, ketone bodies and various mixtures of the two oxidizable substrates. The experiments described above are extended to the enzymatic level - the structural, catalytic and regulatory properties of the acyl CoA dehydrogenase. In these experiments the general acyl CoA dehydrogenase from liver is being used as a model since it is virtually identical to the heart enzyme and can be obtained in excellent yields. The apparent anticooperativity in the enzyme is being investigated by studying the equilibrium binding of a thiolether substrate analog and by conducting redox titrations of the native dehydrogenase and a complex between the enzyme and the thiolether analog, octyl CoA.